CLINICAL PATTERN OF CIRRHOTIC ASCITIES IN THE STATE OF QATAR

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1 QATAR MEDICAL JOURNAL VOL. 17 / NO. 1 / JUNE 2008 ORIGINAL STUDY CLINICAL PATTERN OF CIRRHOTIC ASCITIES IN THE STATE OF QATAR Khan Y.F., Abbas M.T., El Mudathir M., Errayes M., El Hiday A.H. Department of Medicine, Hamad Medical Corporation Doha, Qatar Abstract: Ascites is a common important feature of chronic liver disease and to determine the extent, causes, clinical presentation and nature of cirrhotic ascites in Qatar a descriptive, prospective study was made of 48 males and 14 females with cirrhotic ascites and a mean age of 562 "12.6 years admitted to the Medical Department, Hamad General Hospital between January 2004 and January Twenty six were Qatari, the remainder being of various nationalities. The most common cause of cirrhotic ascites was chronic alcoholism, found in 29 (46.8%) patients. Uncomplicated liver cirrhosis was found in 40 (64.5%) patients, complicated liver cirrhosis in 22 (35.5%) patients. At admission, encephalopathy, GI bleeding, and fever were found to be significantly associated with complicated cirrhotic ascites. Results of the study suggest that cirrhotic ascites is common in the State of Qatar with the most common causes being chronic alcoholism followed by chronic viral hepatitis C and B. It is suggested that efforts are needed to prevent and treat these two conditions. Key words: Alcoholic cirrhosis; cirrhotic ascites; spontaneous bacterial peritonitis. Introduction: Cirrhosis represents a late stage of progressive hepatic fibrosis characterized by distortion of the hepatic architecture and the formation of regenerative nodules. Ascites is the most common complication of liver cirrhosis, occurring in 50% of patients within 10 years of diagnosis of compensated cirrhosis (1). It is a poor prognostic indicator, with a 50% two-year survival (2), worsening significantly to 20% to 50% at one year when the ascites becomes refractory to medical therapy 13,4). Cirrhosis also Address for correspondence: Fahtni Yousef Khan, MD Department of Medicine, Hamad Medical Corporation P.O. Box 3050, Doha Qatar; Fax: fakhanqal@yahoo.co.uk predisposes patients to life-threatening complications such as spontaneous bacterial peritonitis and hepatocellular carcinoma, and therefore is a major indication for liver transplantation. In Qatar liver cirrhosis was the most common cause of ascites, accounting for 59.6% of ascites cases (5). This prospective study was undertaken to describe the causes, clinical presentation and laboratory findings of uncomplicated and complicated cirrhotic ascites in the State of Qatar and to compare the results with previously reported studies. Methods and Patients: This prospective observational hospital-based study was conducted at Hamad Medical Corporation (HMC), State of Qatar, a small country with an area of 11,427 sq. km extending into the Arabian Gulf from the eastern coast of the Arabian Peninsula. According to the 2003 census it has an estimated population of 724,125, with the capital city, Doha, being densely populated. HMC is a tertiary referral center with many hospitals, covering all medical and surgical disciplines including six Intensive Care Units. Free health care for all nationals is the cornerstone of the health care program. In addition expatriates and visitors receive heavily subsidized health care at HMC and a totally free medical service at the Accident and Emergency Department, without requiring any referral from a Primary Health Center. So far, although there are several private hospitals in Doha there are none admitting patients with cirrhotic ascites. This study included all patients who were admitted to the Medical Department of Hamad General Hospital between January 15,2004 and January 14,2005 with a primary diagnosis of cirrhotic ascites and who had peritoneal paracentesis performed within the first 24 hours of admission. Following the taking of a detailed history, a comprehensive clinical examination and the signing of consent, all patients underwent abdominal paracentesis under aseptic conditions using a 22- gauge needle in the left lower abdominal quadrant. The samples of ascitic fluid were sent immediately to the biochemical, cytological and microbiological laboratories for analysis. At the same time, blood samples were taken for 46

2 Khan Y.F., et. al. simultaneous ascitic fluid and blood determination of the levels of total protein, albumin, lactate dehydrogenase (LDH) and glucose. Hepatitis B virus markers and Hepatitis C virus antibodies were checked in all patients. Cirrhotic ascites is ascites in the setting of clinical hepatic failure due to liver cirrhosis and is divided into: ascites due to uncomplicated liver cirrhosis and complicated liver cirrhosis. Complicated liver cirrhosis includes hepatocellular carcinoma and spontaneous bacterial peritonitis (SBP). Diagnosis of liver cirrhosis was reached by clinical assessment, laboratory findings, ultrasonography, and/or other imaging features and when possible by histopathology. Hepatocellular carcinoma (HCC) was diagnosed by a combination of high serum alpha-fetoprotein (> 400 ng/ml) with focal intrahepatic lesion(s) seen by abdominal ultrasound and CT scan of the abdomen and if necessary by histopathology. The diagnosis of spontaneous bacterial peritonitis (SBP) was based on an ascitic fluid white blood cell count of more than 0.5 x 109 cells/l, with a neutrophil count of at least 0.25 x 109 cells/l with or without positive ascitic fluid bacterial culture. Cryptogenic cirrhosis is defined as cirrhosis of unknown etiology despite extensive examinations and tests, while undetermined cirrhosis is defined as cirrhosis of unknown etiology that is not investigated completely. Data analysis: Statistical analysis was carried out using the software Epilnfo2000. Quantitative variables are expressed as mean" standard deviations. Student T-test was used for continuous variables and Mann-Whitney U-test if variables that Were not normally distributed. Fisher exact test or Chi-Square test were used when appropriate to compare Qatari versus non- Qatari patients in respect to the etiology of cirrhotic ascites and to compare complicated versus uncomplicated cirrhotic ascites in respect to their clinical presentations. Results were considered significant if the p-value was less than Results: Of 62 patients in the study 48 (77.4%) were male and 14 (22.6%) female with a mean age of 56.2" 12.6 years. Twentysix (42%) were Qatari and the 36 non-qataris (58%) comprised ten (16.1%) Egyptians, eight (13%) Pakistani, three (4.8%) Sudani, three (4.8%) Bangladeshi, two each (3.2%) Iranian, Palestinian, Jordanian, Indian, Saudi, and one each (1.6%) from the Philippines and Yemen. Forty (64.5%) had uncomplicated liver cirrhosis and twenty-two had complicated liver cirrhosis, eleven (17.7%) due to HCC and eleven due to SBP. Chronic alcoholism was found in 29 (46.8%) patients. Other causes Were chronic viral hepatitis Type C in 16 (25.8%) patients, chronic viral hepatitis Type B in eight (12.9%) patients and miscellaneous causes in nine (14.5%) patients, including cryptogenic cirrhosis, autoimmune hepatitis, Wilson's disease and hemochromatosis. Table 1 shows the causes of cirrhotic ascites in relation to sex and nationality. Table 1: Causes of Cirrhotic Ascites Causes Qatari N(%) Non-Qatari N(%) Total % p value Alcoholism 15/0 14/0 29(46.8) 0.22 ns HCV 1/4 8/3 16(25.8) 0.47 ns HBV 1/2 4/1 8(12.9) ns Miscellaneous Cryptogenic 0/1 1/1 3(4.9) 1.00 ns Autoimmune 0/1 1/0 2(3.2) 1.00 ns Wilson's disease 0/0 1/0 1(1.6) Hemochromatosis 0/0 1/0 1(1.6) Undetermined 0/0 1/0 2(3.2) Clinical Presentation: On admission, encephalopathy, GI bleeding, and fever were found to be significantly associated with SBP and HCC; moreover, although the prevalence of tense ascites and abdominal pain at time of admission tended to be lower in patients with uncomplicated cirrhotic ascites, the difference was not significant (table 2). In the subgroup of uncomplicated cirrhotic ascites, six (15%) patients had Child-Pugh class A, 31(77.5%) class B and three (7.5%) class C. All patients with SBP and HCC had evidence of advanced liver disease: Twelve patients (54.5%) were in Child-Pugh class B and 10 patients (45.5%) in Child-Pugh class C. The baseline characteristics of the cirrhotic patients with and without complications are shown in Table 2. Ascitic fluid characteristics of uncomplicated cirrhosis, SBP, and HCC are shown in Table 3. Abdominal ultrasound showed an enlarged spleen in all patients and chest x-rays revealed pleural effusion in 12 (19.4%) patients; right-sided in nine of these (75%), left-sided in one (8.4%), and bilateral in two (16.6%). Upper gastrointestinal endoscopy showed esophageal varices of different grades in 49 (79.1%) patients. Ascitic fluid cultures were negative in six (54.5%) patients with SBP, while bacterial isolates were recovered from five (45.5%) patients. The most common microorganism isolated was Escherichia coli; found in three patients while klebsiella pneumoniae was isolated from one patient and Vibrio cholerae non-ol non-0139 from another. Etiologic factors of cirrhosis in patients with HCC included, chronic hepatitis C in five (8%) patients, alcoholic liver cirrhosis in three (4.8%), chronic hepatitis B in two (3.2%), and cryptogenic in one (1.6%). QATAR MEDICAL JOURNAL VOL. I7 / NO. I / JUNE

3 Khan Y.F., et. al Within the next twelve months seven patients died (a casefatality rate of 11.3 %) due to HCC in three (4.8%) patients, gastrointestinal bleeding in two (3.2%), SBP in one (1.6%), and hepatic failure in one (1.6%), Discussion: In this study the most common cause of cirrhotic ascites was chronic alcoholism, which is comparable with reports from Table II. Comparison between complicated and uncomplicated liver cirrhosis Variables Uncomplicated liver cirrhosis (40) Complicated cirrhosis (SBP&HCC) (22) p value Age ns Sex (M/F) (48/14) 30/10 18/4 Causes of admission Tense ascites 18 (45%) 13(59.1) 0.42 ns Abdominal pain 6 (15%) 8 (22%) ns Encephalopathy 8 (20%) 11 (50%) 0.03 GI bleeding 6(15%) 10 (45.5%) Fever 2 (5%) 11 (50%) Child-Pugh A 6 (15%) 0 (0%) B 31 (77.5%) 12 (54.5%) 0.112ns C 3 (7.5%) 10(45.5%) Investigations White blood cells (x 10 9 /L) Hemoglobin (g/dl) ns Platelets (x 10 9 /L) ns Creatinine (pmol/l) ns Sodium (meq/l) T. bilirubin (pmol/l Albumen (g/dl) ns SGPT (ALT) U/L ns SGOT(AST) U/L ns INR One year mortality rate (%) '1 (2.5%) 6 (27.3%) western countries (6 " 9), but different from those reported in Saudi Arabia (10,12). Surprisingly, chronic alcoholism among Qatari patients accounted for 57.7% of patients with cirrhotic ascites. Chronic hepatitis C was present in 66.7 % of patients with viral cirrhotic ascites, which coincides with studies conducted in Egypt and United States (13,14), but differs from those in other Asian countries (11 ' 15). Not surprisingly, seven of these patients were Egyptian. The reason for the prevalence of chronic hepatitis C in Egyptian patients could be attributed to the hypothesis that past mass parenteral chemotherapy campaigns for schistosomiasis facilitated HCV transmission (13). Globally, the prevalence of SBP among cirrhotic patients with ascites ranges between 10% and 30% (6 ~ 201). In our study, the prevalence of SBP was 17.7%, which falls within the global range. On the other hand, the reported incidence of HCC in cirrhotic patients, in both eastern and western studies, varied between 3% and 6.5% per year of follow up (2128). In our study HCC occurred in 17.7% of cirrhotic patients. In cirrhotic patients SBP and HCC remain serious complications that need early diagnosis and management to reduce morbidity and mortality. As noted in our study, encephalopathy, GI bleeding, and fever were found to be significantly associated with SBP and HCC, as well as high leukocyte levels, high bilirubin and high INR. Hence, clinical presentations of cirrhotic ascites can be used as a clue for early suspicion of these complications. Abdominal ultrasound study showed enlarged spleen in all patients, which is consistent with other reports. The cause of splenomegaly in cirrhotic patients is possibly due to the hemodynamic changes associated with portal hypertension (PH) (29) of which it is an important sign although the size of the spleen does not correlate with the degree of increased portal pressure (30). In some studies esophageal varices were found in 44%- 83% of cirrhotic patients (31 ' 33). Upper endoscopy showed esophageal varices of different grades in 79.1% of our patients, falling within the above range. The frequency of hepatic hydrothorax in cirrhotic patients is reported to be around five per cent (34) with the pleural effusion being predominantly rightsided (85% of cases) but may be bilateral (35), whereas in our Table III: Cirrhotic ascites fluid characteristics Protein SAAG LDH Glucose Cells/!L (g/dl) (g/dl) (U/L) (mmol/l) RBC WBC Uncomplicated cirrhosis 1.6" " " " 1.12 <100 < 500 neutrophils SBP 2.1" " " " 2.22 <100 < 500 neutrophils HCC 1.5" " " " 2 <100 < 500 neutrophils 48 QATAR MEDICAL JOURNAL VOL. 17 / NO. 1 / JUNE 2008

4 Khan Y.F., et. al. study, chest x-ray study revealed pleural effusion in 12 (19.4%) patients; right-sided in nine (75%) patients, left-sided in one (8.4%), bilateral in two (16.6%). Biochemical study of ascitic fluid was of limited diagnostic value in the differentiation of various types of cirrhotic ascites but microscopic and bacteriological examinations of ascitic fluid were of value in diagnosing SBP; the ascitic fluid polymorphonuclear cell count being the most sensitive test for evaluating infection. Cultures of the ascitic fluid are helpful in identifying the organism and are best performed by bedside injection into blood culture bottles (36). In the present study, six (54.5%) positive cultures were obtained from the eleven cases of SBP. It is possible that this low rate was due to suboptimal culturing methods and techniques. However, low rates of positive SBP cultures have been reported also in other studies, with proportions ranging from 39% to 59% (37 40), and these findings probably reflect earlier diagnosis of the infection. Cytological study of ascitic fluid, with a zero yield, was of limited value in the diagnosis of HCC. Although antibiotic therapy produces a good response, the mortality from SBP remains high at approximately 30%- 50% (41 ' 42). As mentioned before cirrhotic ascites is a poor prognostic indicator, with a 50% two-year survival, worsening significantly to 20% to 50% at one year when the ascites becomes refractory to medical therapy. The one-year mortality in our study was 11.3%, consistent with other reports (3,4,8). In conclusion, chronic alcoholism and chronic viral hepatitis (B and C) were the main causes of cirrhotic ascites in Qatar, accounting for 85% of cirrhotic ascites. To reduce the burden, morbidity and mortality of cirrhotic ascites, efforts should be directed towards prevention and treatment of alcoholic and viral cirrhosis. For healthy persons prevention of cirrhosis can be achieved by avoiding alcohol completely. There is now an effective vaccine against Type B hepatitis that is given routinely to toddlers as part of their immunization schedule in Qatar. So far, no vaccination against C hepatitis virus is available but transmission can be avoided by using disposable needles in hospitals, by strict and universal screening of all blood donors in blood banks and by refusing donations from infected persons. In chronic hepatitis or cirrhosis, irrespective of the etiology, all patients should be advised to abstain from alcohol completely, including avoidance of alcohol-containing medications and socalled "nonalcoholic" beers (43). A timely liver transplant can prevent cancer development in this group of patients. References: 1. 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